tbuckley/cabot-search huggingface dataset:
Oral Exposure to Polystyrene Microplastics of Mice on a Normal or High-Fat Diet and Intestinal and Metabolic Outcomes
Authors: Takuro Okamura, Masahide Hamaguchi, Yuka Hasegawa, Yoshitaka Hashimoto, Saori Majima, Takafumi Senmaru, Emi Ushigome, Naoko Nakanishi, Mai Asano, Masahiro Yamazaki, Ryoichi Sasano, Yuki Nakanishi, Hiroshi Seno, Hirohisa Takano, Michiaki Fukui
Journal: Environmental Health Perspectives (2023)

Microplastics (MPs) are small particles of plastic (≤5mm in diameter). In recent years, oral exposure to MPs in living organisms has been a cause of concern. Leaky gut syndrome (LGS), associated with a high-fat diet (HFD) in mice, can increase the entry of foreign substances into the body through the intestinal mucosa.We aimed to evaluate the pathophysiology of intestinal outcomes associated with consuming a high-fat diet and simultaneous intake of MPs, focusing on endocrine and metabolic systems.C57BL6/J mice were fed a normal diet (ND) or HFD with or without polystyrene MP for 4 wk to investigate differences in glucose tolerance, intestinal permeability, gut microbiota, as well as metabolites in serum, feces, and liver.In comparison with HFD mice, mice fed the HFD with MPs had higher blood glucose, serum lipid concentrations, and nonalcoholic fatty liver disease (NAFLD) activity scores. Permeability and goblet cell count of the small intestine (SI) in HFD-fed mice were higher and lower, respectively, than in ND-fed mice. There was no obvious difference in the number of inflammatory cells in the SI lamina propria between mice fed the ND and mice fed the ND with MP, but there were more inflammatory cells and fewer anti-inflammatory cells in mice fed the HFD with MPs in comparison with mice fed the HFD without MPs. The expression of genes related to inflammation, long-chain fatty acid transporter, and Na+/glucose cotransporter was significantly higher in mice fed the HFD with MPs than in mice fed the HFD without MPs. Furthermore, the genus Desulfovibrio was significantly more abundant in the intestines of mice fed the HFD with MPs in comparison with mice fed the HFD without MPs. Muc2 gene expression was decreased when palmitic acid and microplastics were added to the murine intestinal epithelial cell line MODE-K cells, and Muc2 gene expression was increased when IL-22 was added.Our findings suggest that in this study, MP induced metabolic disturbances, such as diabetes and NAFLD, only in mice fed a high-fat diet. These findings suggest that LGS might have been triggered by HFD, causing MPs to be deposited in the intestinal mucosa, resulting in inflammation of the intestinal mucosal intrinsic layer and thereby altering nutrient absorption. These results highlight the need for reducing oral exposure to MPs through remedial environmental measures to improve metabolic disturbance under high-fat diet conditions. https://doi.org/10.1289/EHP11072.
Impact of a Statewide Livestock Antibiotic Use Policy on Resistance in Human Urine <i>Escherichia coli</i> Isolates: A Synthetic Control Analysis
Authors: Joan A. Casey, Sara Y. Tartof, Meghan F. Davis, Keeve E. Nachman, Lance Price, Cindy Liu, Kalvin Yu, Vikas Gupta, Gabriel K. Innes, Hung Fu Tseng, Vivian Do, Alice R. Pressman, Kara E. Rudolph
Journal: Environmental Health Perspectives (2023)

Background: On 1 January 2018, California implemented Senate Bill 27 (SB27), banning, for the first time in the United States, routine preventive use of antibiotics in food-animal production and any antibiotic use without a veterinarian's prescription. Objectives: Our objective was to assess whether SB27 was associated with decreased antimicrobial resistance among E. coli isolated from human urine. Methods: We used U.S. nationwide monthly state-level data from BD Insights Research Database (Becton, Dickinson, and Co.) spanning 1 January 2013 to 30 June 2021 on antibiotic-resistance patterns of 30-d nonduplicate E. coli isolated from urine. Tested antibiotic classes included aminoglycosides, extended-spectrum cephalosporins (ESC), fluoroquinolones, and tetracyclines. Counts of tested and not-susceptible (resistant and intermediate, hereafter resistant) urine isolates were available by sex, age group (<65, 65+ year), month, and state. We applied a synthetic control approach to estimate the causal effect of SB27 on resistance patterns. Our approach created a synthetic California based on a composite of other states without the policy change and contrasted its counterfactual postpolicy trends with the observed postpolicy trends in California. Findings: We included 7.1 million E. coli urine isolates, 90% among women, across 33 states. From 2013 to 2017, the median (interquartile range) resistance percentages in California were 11.9% (7.4, 17.6), 13.8% (5.8, 20.0), 24.6% (9.6, 36.4), 7.9% (2.1, 13.1), for aminoglycosides, ESC, fluoroquinolones, and tetracyclines, respectively. SB27 was associated with a 7.1% reduction in ESC resistance (p-value for joint null: <0.01), but no change in resistance to aminoglycosides, fluoroquinolones, or tetracyclines. Discussion: Further research is needed to determine the role of SB27 in the observed reduction in ESC resistance E. coli in human populations, particularly as additional states implement similar legislation. https://doi.org/10.1289/EHP11221
The gut microbiota promotes distal tissue regeneration via RORγ+ regulatory T cell emissaries
Authors: Bola S. Hanna, Gang Wang, Silvia Galván-Peña, Alexander O. Mann, Ricardo N. Ramirez, Andrés R. Muñoz-Rojas, Kathleen Smith, Min Wan, Christophe Benoist, Diane Mathis
Journal: Immunity (2023)
Metabolic Signatures of Youth Exposure to Mixtures of Per- and Polyfluoroalkyl Substances: A Multi-Cohort Study
Authors: Jesse A. Goodrich, Douglas I. Walker, Jingxuan He, Xiangping Lin, Brittney O. Baumert, Xin Hu, Tanya L. Alderete, Zhanghua Chen, Damaskini Valvi, Zoe C. Fuentes, Sarah Rock, Hongxu Wang, Kiros Berhane, Frank D. Gilliland, Michael I. Goran, Dean P. Jones, David V. Conti, Leda Chatzi
Journal: Environmental Health Perspectives (2023)

Exposure to per- and polyfluoroalkyl substances (PFAS) is ubiquitous and has been associated with an increased risk of several cardiometabolic diseases. However, the metabolic pathways linking PFAS exposure and human disease are unclear.
T cell-mediated targeted delivery of tadalafil regulates immunosuppression and polyamine metabolism to overcome immune checkpoint blockade resistance in hepatocellular carcinoma
Authors: Xiaobin Wang, Qiaoyun Zhang, Jingwen Zhou, Zecong Xiao, Jianxin Liu, Shaohui Deng, Xiaoyang Hong, Wensou Huang, Mingyue Cai, Yongjian Guo, Jingjun Huang, Yong Wang, Liteng Lin, Kangshun Zhu
Journal: Journal for ImmunoTherapy of Cancer (2023)

Immune checkpoint blockade (ICB) monotherapy provides poor survival benefit in hepatocellular carcinoma (HCC) due to ICB resistance caused by immunosuppressive tumor microenvironment (TME) and drug discontinuation resulting from immune-related side effects. Thus, novel strategies that can simultaneously reshape immunosuppressive TME and ameliorate side effects are urgently needed. Both in vitro and orthotopic HCC models were used to explore and demonstrate the new role of a conventional, clinically used drug, tadalafil (TA), in conquering immunosuppressive TME. In detail, the effect of TA on M2 polarization and polyamine metabolism in tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) was identified. After making clear the aforementioned immune regulatory effect of TA, we introduced a nanomedicine-based strategy of tumor-targeted drug delivery to make better use of TA to reverse immunosuppressive TME and overcome ICB resistance for HCC immunotherapy. A dual pH-sensitive nanodrug simultaneously carrying both TA and programmed cell death receptor 1 antibody (aPD-1) was developed, and its ability for tumor-targeted drug delivery and TME-responsive drug release was evaluated in an orthotopic HCC model. Finally, the immune regulatory effect, antitumor therapeutic effect, as well as side effects of our nanodrug combining both TA and aPD-1 were analyzed. TA exerted a new role in conquering immunosuppressive TME by inhibiting M2 polarization and polyamine metabolism in TAMs and MDSCs. A dual pH-sensitive nanodrug was successfully synthesized to simultaneously carry both TA and aPD-1. On one hand, the nanodrug realized tumor-targeted drug delivery by binding to circulating programmed cell death receptor 1-positive T cells and following their infiltration into tumor. On the other hand, the nanodrug facilitated efficient intratumoral drug release in acidic TME, releasing aPD-1 for ICB and leaving TA-encapsulated nanodrug to dually regulate TAMs and MDSCs. By virtue of the combined application of TA and aPD-1, as well as the efficient tumor-targeted drug delivery, our nanodrug effectively inhibited M2 polarization and polyamine metabolism in TAMs and MDSCs to conquer immunosuppressive TME, which contributed to remarkable ICB therapeutic efficacy with minimal side effects in HCC. Our novel tumor-targeted nanodrug expands the application of TA in tumor therapy and holds great potential to break the logjam of ICB-based HCC immunotherapy.
Contribution of heterozygous PCSK1 variants to obesity and implications for precision medicine: a case-control study
Authors: Lise Folon, Morgane Baron, Bénédicte Toussaint, Emmanuel Vaillant, Mathilde Boissel, Victoria Scherrer, Hélène Loiselle, Audrey Leloire, Alaa Badreddine, Beverley Balkau, Guillaume Charpentier, Sylvia Franc, Michel Marre, Soulaimane Aboulouard, Michel Salzet, Mickaël Canouil, Mehdi Derhourhi, Philippe Froguel, Amélie Bonnefond
Journal: The Lancet Diabetes & Endocrinology (2023)
Metabolic Modulation
Authors: Gary D. Lopaschuk, Ivan M. Rebeyka, Michael F. Allard
Journal: Circulation (2002)

eart failure is a clinical syndrome characterized by progressive deterioration of heart pump function that is very common in our society. 1It is a highly lethal disease with an annual mortality rate ranging from 5% to 10% in those with mild symptoms to 30% to 40% in those with severe symptoms. 1The morbidity associated with heart failure is also substantial such that heart failure is currently the leading cause of hospitalization in the United States, with direct costs related to treatment amounting to $20 000 million annually. 1,2As a result, the socioeconomic impact of heart failure is great.The need to prevent and, when necessary, effectively treat heart failure is, therefore, of utmost importance.
Prevention of Venous Thromboembolism Following Total Hip Replacement
Authors: William H. Harris
Journal: JAMA (1972)

In a prospective randomized study of thromboembolic disease following total hip replacement in 227 patients, the efficacy and safety of prophylaxis by warfarin sodium has been compared with that afforded by dextran 40. No fatal pulmonary emboli occurred. No statistically significant differences existed between the two agents in terms of the frequency of clinically detectable venous thrombosis or pulmonary embolism. Thromboembolic disease occurred in 7.9% of the patients given warfarin and in 10% of the patients given dextran 40. Significant wound bleeding was infrequent and equal in both groups. These two drugs appear equally effective in providing prophylaxis against venous thromboembolic disease following total hip replacement.
Odptic Neuropathy in Relapsing Polychondritis
Authors: Paul J. Killian
Journal: JAMA (1978)

RELAPSING polychondritis is a rare disorder of uncertain origin characterized by recurrent inflammation of cartilaginous structures throughout the body. An increased awareness has resulted in more frequent reporting of this condition in recent years. Ocular involvement occurs in 65% of patients with relapsing polychondritis.<sup>1</sup>Episcleritis is the most common ocular finding, although scleritis, conjuctivitis, iritis, and keratitis are frequently found. Rarely, chorioretinitis, exophthalmos, extraocular muscle palsies, and optic neuritis may be encountered. We report the case of a 63-year-old man with relapsing polychondritis in whom ischemic optic neuropathy developed. <h3>Report of a Case</h3> A 63-year-old man noted the rapid onset of decreased vision in his left eye. He also complained of shoulder girdle myalgias. He was seen at a nearby emergency room, was thought to have unilateral papilledema, and was transferred to Walter Reed Army Medical Center. Initial examination showed that his visual acuity was 20/20 in the right
A gel microparticle-based self-thickening strategy for 3D printing high-modulus hydrogels skeleton cushioned with PNAGA hydrogel mimicking anisotropic mechanics of meniscus
Authors: Ziyang Xu, Qian Zhang, Chuanchuan Fan, Meng Xiao, Rong Yang, Yuan Yao, Yang Wu, Xiongfeng Nie, Hongying Wang, Wenguang Liu
Journal: Bioactive Materials (2023)

Developing a meniscus substitute mimicking the anisotropic mechanics (higher circumferential tensile modulus and lower compressive modulus) of native tissue remains a great challenge. In this work, based on the pendant group structure-dependent H-bonding strengthening mechanism, two kinds of amide-based H-bonding crosslinked hydrogels with distinct mechanical behaviors, that is, the flexible poly(N-acryloyl glycinamide) (PNAGA) and the ultra-stiff poly(N-acryloylsemicarbazide) (PNASC) hydrogels are employed to construct the biomimetic meniscus substitute. To this end, a gel microparticle-based self-thickening strategy is first proposed to fabricate PNASC (GMP-PNASC) high-modulus hydrogels skeleton by extrusion printing technology in mimicking the collagen fibers in native meniscus to resist the circumferential tensile stress. Then, the PNAGA hydrogel is infused into the PNASC skeleton to replicate the proteoglycan, providing a lower compressive modulus. By regulating the structural features at the interior and peripheral regions, the GMP-PNASC/PNAGA hydrogel meniscus scaffold with the higher tensile modulus (87.28 ± 6.06 MPa) and lower compressive modulus (2.11 ± 0.28 MPa) can be constructed. In vivo outcome at 12 weeks post-implantation of rabbit's medial meniscectomy model confirms the effects of GMP-PNASC/PNAGA meniscus scaffold on alleviating the wear of articular cartilage and ameliorating the development of osteoarthritis (OA).
Study: No New SARS-CoV-2 Variants in Recent Outbreak in China
Authors: Emily Harris
Journal: JAMA (2023)

Study: No New SARS-CoV-2 Variants in Recent Outbreak in China After relaxing its "zero-COVID policy" in early December 2022, China's SARS-CoV-2 infections surged, stoking concerns that new variants might appear.But none emerged in a genomic analysis of 413 COVID-19 cases collected in Beijing between November 14 and December 20, 2022.Two Omicron subvariants-BA.5.2 and BF.7-represented more than 90% of local infections, researchers in China reported in The Lancet.The authors of a corresponding editorial noted that because the study only covered cases from a few weeks after China's policy change, it would not have detected variants that might have emerged later.They also emphasized that the study cases were in Beijing and might not reflect conditions in other regions of China.
Long-term outcomes of patients with COVID-19 treated with helmet noninvasive ventilation or usual respiratory support: follow-up study of the Helmet-COVID randomized clinical trial
Authors: Yaseen M. Arabi, Hasan M. Al-Dorzi, Sara Aldekhyl, Saad Al Qahtani, Sheryl Ann Abdukahil, Eman Al Qasim, Mohammad Khulaif Al Harbi, Ayman Kharaba, Talal Albrahim, Mohammed S. Alshahrani, Abdulrahman A. Al-Fares, Ali Al Bshabshe, Ahmed Mady, Zainab Al Duhailib, Haifa Algethamy, Jesna Jose, Mohammed Al Mutairi, Omar Al Zumai, Hussain Al Haji, Ahmed Alaqeily, Wedyan Al Wehaibi, Zohair Al Aseri, Awad Al-Omari, Haytham Tlayjeh, Abdulaziz Al-Dawood, Yaseen M. Arabi, Hasan M. Al-Dorzi, Haytham Tlayjeh, Sara Aldekhyl, Saad Al-Qahtani, Mohammed Khulaif Al-Harbi, Mohammad Al-Mutairi, Hussain Al-Haji, Omar Al-Zumai, Ahmed Alaqeily, Sheryl Ann Abdukahil, Eman Al-Qasim, Jesna Jose, Yaseen M. Arabi, Hasan Al-Dorzi, Sheryl Ann Abdukahil, Nicholas Hill, Stefano Nava, James Mojica, Michael Harhay, Abdulrahman Al-Fares, Ahmed Almumin, James Albert, Israr Khan, Muhammad Ayaz, Ali Al Bshabshe, Munir Mustafa Aldammad, Nasser M. Alwadai, Om Prakash Palanivel, Yaseen M. Arabi, Hasan M. Al-Dorzi, Haytham Tlayjeh, Mohammad Al Harbi, Sara Aldekhyl, Saad Al Qahtani, Abdulaziz Al-Dawood, Sheryl Ann I. Abdukahil, Eman Al Qasim, Jesna Jose, Wedyan Al Wehaibi, Musharaf Sadat, Lara Afesh, Felwa Bin Humaid, Mohammad Al Mutairi, Hussain Al Haji, Omar Al Zumai, Ahmed Alaqeily, Yassin Ismaiel, Faisal Al Baseet, Mohammad Al Obaidi, Edgardo Tabhan, Rami Al Khalid, Omar Al Fares, Abdullah Al Suayb, Hashem Sammanoudi, Victoria Burrows, Amal Matroud, Brintha Naidu, Haifa Algethamy, Sheryl Lungue, Liyakat Khan, Moataz Jaber, Saleh Baaziz, Shehla Nuzhat, Mohammed S. Alshahrani, Talal Ali Albrahim, Laila Perlas Asonto, Charlene Mapusao, Arivukodhi Muthu, Abdulaziz Saad AlGhamdi, Carmelo Angala, Ayman Kharaba, Mohamed Hussien, Ahmad AlFar, Salman Al Asiri, Anas Al Solami, Zainab Al Duhailib, Mahmoud Abu Riash, Haya Al Othaimeen, Rozeena Huma, Ahmed Mady, Naif Abdulrahman Aldosari, Khalid Abdullah Alreyes, Arul Prasath Lakshmanan, Alzahra Al Obaed, Mobarak Almushhen, Fhausia Hali, Ika Fibriantini, Bobby Rose Marasigan, Katrina Baguisa, Saleh Ali Almahwi, Jamal Chalabi, Fahad Al-Hameed, Abdulhadi Bin Eshaq, Rakan Alqahtani, Omar Alnafel, Zohair Al Aseri, Awad Al-Omari
Journal: Intensive Care Medicine (2023)
Phenotypic characterization of disease‐initiating stem cells in <i>JAK2</i>‐ or <i>CALR</i>‐mutated myeloproliferative neoplasms
Authors: Daniel Ivanov, Jelena D. Milosevic Feenstra, Irina Sadovnik, Harald Herrmann, Barbara Peter, Michael Willmann, Georg Greiner, Katharina Slavnitsch, Emir Hadzijusufovic, Thomas Rülicke, Maik Dahlhoff, Gregor Hoermann, Sigrid Machherndl‐Spandl, Gregor Eisenwort, Michael Fillitz, Thamer Sliwa, Maria‐Theresa Krauth, Peter Bettelheim, Wolfgang R. Sperr, Elisabeth Koller, Michael Pfeilstöcker, Heinz Gisslinger, Felix Keil, Robert Kralovics, Peter Valent
Journal: American Journal of Hematology (2023)

Myeloproliferative neoplasms (MPN) are characterized by uncontrolled expansion of myeloid cells, disease-related mutations in certain driver-genes including JAK2, CALR, and MPL, and a substantial risk to progress to secondary acute myeloid leukemia (sAML). Although behaving as stem cell neoplasms, little is known about disease-initiating stem cells in MPN. We established the phenotype of putative CD34
Covid-19: Death rate gap for ethnic minorities closes, ONS data show
Authors: Jacqui Wise
Journal: BMJ (2023)

Covid-19: Death rate gap for ethnic minorities closes, ONS data show Jacqui WiseThere is no longer evidence of higher covid-19 mortality among ethnic minority groups compared with white people in England, latest data 1 from the Office for National Statistics (ONS) show.The news was welcomed, but a small increase in covid-19 mortality in the white British group during 2022 was described as "worrying" by healthcare think tank the King's Fund.
Integrated circulating tumor DNA and T cell repertoire predict radiotherapeutic response and outcome in non‐small cell lung cancer patients with brain metastasis
Authors: Ling Peng, Yawen Bin, Peng Ding, Lingjuan Chen, Hao Zeng, Zelong Xu, Liyan Ji, Xuan Gao, Pian Liu, Ye Wang, Sheng Zhang, Zhongxing Liao, Xuefeng Xia, Ruiguang Zhang, Fan Tong, Xiaorong Dong
Journal: Cancer Communications (2023)

Integrated circulating tumor DNA and T cell repertoire predict radiotherapeutic response and outcome in non-small cell lung cancer patients with brain metastasisDear editor, The scarcity of routine metastatic biopsies or resection limits the finding of biomarkers of diagnosis and prognosis in patients with brain metastases.Derived from necrosis, apoptosis, and secretion of tumor cells, circulating tumor DNA (ctDNA) is widely distributed in various body fluids, including peripheral blood and cerebrospinal fluid (CSF), as an alternative biomarker for tumor-associated analysis [1].Fortunately, genomic alterations of blood ctDNA and CSF ctDNA have been proven as prognostic markers in non-small cell lung cancer (NSCLC) patients with brain metastasis [2,3].T cell-mediated immunity is critical in suppressing oncogenesis and metastasis of NSCLC.Targeted sequencing in the highly variable complementarity-determining region 3 (CDR3) region of the beta chain of the T cell repertoire (TCR) provides a robust method to quantify T cell diversity [4].Casarrubios et al. [5] reported that the evenness of pretreatment TCR was related to the clinical response of NSCLC patients receiving neoadjuvant chemotherapy plus immunotherapy.Radiotherapy may stimulate immune responses against malignancies.Locally, irradiation causes antigen exposure by directly destroying cancer cells, which activates both the local and systemic immune systems.Irradiation can also cause DNA damage, and the ensuing mutations in cells with DNA mismatch repair deficiencies might increase the load of neoantigens, triggering an immunological response [6].The PACIFIC trial demonstrated that combining radiotherapy and immunotherapy was effective in prolonging
Sepsis-associated acute kidney injury: consensus report of the 28th Acute Disease Quality Initiative workgroup
Authors: Alexander Zarbock, Mitra K. Nadim, Peter Pickkers, Hernando Gomez, Samira Bell, Michael Joannidis, Kianoush Kashani, Jay L. Koyner, Neesh Pannu, Melanie Meersch, Thiago Reis, Thomas Rimmelé, Sean M. Bagshaw, Rinaldo Bellomo, Vicenzo Cantaluppi, Akash Deep, Silvia De Rosa, Xose Perez-Fernandez, Faeq Husain-Syed, Sandra L. Kane-Gill, Yvelynne Kelly, Ravindra L. Mehta, Patrick T. Murray, Marlies Ostermann, John Prowle, Zaccaria Ricci, Emily J. See, Antoine Schneider, Danielle E. Soranno, Ashita Tolwani, Gianluca Villa, Claudio Ronco, Lui G. Forni
Journal: Nature Reviews Nephrology (2023)
A “one-size-fits-most” walking recognition method for smartphones, smartwatches, and wearable accelerometers
Authors: Marcin Straczkiewicz, Emily J. Huang, Jukka-Pekka Onnela
Journal: npj Digital Medicine (2023)

The ubiquity of personal digital devices offers unprecedented opportunities to study human behavior. Current state-of-the-art methods quantify physical activity using "activity counts," a measure which overlooks specific types of physical activities. We propose a walking recognition method for sub-second tri-axial accelerometer data, in which activity classification is based on the inherent features of walking: intensity, periodicity, and duration. We validate our method against 20 publicly available, annotated datasets on walking activity data collected at various body locations (thigh, waist, chest, arm, wrist). We demonstrate that our method can estimate walking periods with high sensitivity and specificity: average sensitivity ranged between 0.92 and 0.97 across various body locations, and average specificity for common daily activities was typically above 0.95. We also assess the method's algorithmic fairness to demographic and anthropometric variables and measurement contexts (body location, environment). Finally, we release our method as open-source software in Python and MATLAB.